Lecture - 27
Chromosomal & genetics disorders, inbreeding
[FL] In today’s class we will have a look at chromosomal and genetic disorders and inbreeding.
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Now, chromosome as we have seen in one of the lectures before.
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Chromosome; so chroma is colour and some is body. So, in any of our cells we have a nucleus and inside this nucleus, we have these fragments that contain all are genetic information and these are known as chromosomes. Now chromosomal disorders are defined like this; a chromosome disorder is a missing extra or irregular portion of chromosomal DNA, caused by an a typical number of chromosomes or a structural abnormality in one or more chromosomes.
So, what do we see here? Either there is some part that is missing some part that is extra or some part that is irregular in the chromosomal DNA and this can be caused because of a typical number of chromosomes i.e. incorrect number of chromosomes or a structural abnormality in one or more chromosomes.
So, what are all things can we see here?
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We can observe things like numerical disorders. So, all of our chromosomes are here in pairs. So, for instance, if you talk about chromosome number18, there would be one chromosome 18 that comes from the father and one chromosome 18 that comes from the mother and this phenomenon is known as Bisomy. So, bi is two and soma is body. So, there are two bodies of every chromosome that are present in the cell. Now numerical disorders include Monosomy. So, mono is one somy is body. So, there is only one chromosome in place of a pair of chromosomes. Then we can have Trisomy. So, in place of two chromosomes we can have three chromosomes. Tetrasomy in which in place of two chromosomes you can have four chromosomes and so on. So, these are known as numerical disorders.
We even have a situation that is known as Nullsomy. So, Nullsomy would mean that in place of a pair of chromosomes, you do not have any chromosome that belongs to that pair. So, for instance, chromosome number 18 could be missing from any cell or any organism.
So, these are numerical disorders next we have structural abnormalities. Structural abnormalities include deletion, duplication, translocation, and inversion. So, division means that a part of a chromosome is missing.
So, for instance, if this is your chromosome, then it is possible that this portion is missing and so, your chromosome will become shorten.
So, this position is missing and then it just has the other end. So, it is shortened up. So, this is a deletion a part of a chromosome that is missing. Next we have duplication; a part of a chromosome in two or multiple copies. So, let us represent this with different colour.
So, let us call this as the red region, this is the blue region and say, this is the yellow region. Now in the first case what we had was that we have that red region and the yellow region and the blue region was missing, so this a deletion. Now in the case of duplication, what we can have is that, we have this chromosome; the red region is there then we have a blue region that comes that as duplicated. So, it has increase units length and then we have the yellow region.

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So, in this case we will see that, this is the red region, then we have one blue region and then we have another blue region and then we have the yellow region. So, this would be known as duplication because this region of the chromosome is present in two copies. Now in place of two copies we can have even multiple copies. Next is translocation. So, translocation is that a part of a chromosome gets shifted to another chromosome.
So, in that case, let us take another chromosome, and in this chromosome we have say, the purple colour, followed by light green colour, followed by say, pink colour. So now, in the case of a translocation, we could have a situation in which say this portion gets translocated this portion is getting translocated.
So, that would result in a situation in which the first chromosome and we have the second chromosome. So, the first one now has the purple region on the top, followed by the light green region, followed by the yellow region, because these two portions got translocated from one to the other and so, the second one would have the red region followed by the blue region and then followed by the pink region. So, this thing is known as a translocation.
So, a part of a chromosome has shifted to another chromosome. And the fourth situation is inversion. So, in the case of an inversion, suppose we are talking about this chromosome only. So, in the case of inversion it is possible that these two portions get interchanged.
So, in this situation, what we will have is that, in this chromosome we have the top is the red region, followed by the yellow region, followed by the blue region. So, what has happened in this case is that, this portion of this chromosome it is turned upside down. Now, it is not necessary that this should only occur in the end of the chromosome, but it can occur somewhere in between as well. So, for instance, in the red portion we can have a situation that this portion gets upside down.
So, such a situation will be known as an inversion. Now why are all of these important? Now chromosomes contain DNA that has all the genes. Now if there is a situation in which there is a deletion of a part of a chromosome, then it is possible that some genes, maybe a single gene or a set of genes they are deleted along with this part of the chromosome.
So, in that case, any of the functions that were being done by that gene will now no longer be in the organism. So, it is possible that there would be some proteins that are now completely missing from the animal. So, that may lead to a disease or that might lead to death. Duplication; a part of a chromosome is in two or multiple copies.
So, if there was a gene that was performing a function so, there was a gene that was producing some protein. So, we had a gene that was producing protein.
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And let us say that it was producing x amount of protein. Let us call it x milli grams of protein. Now if you have two times of this gene then it may produce two times of the protein. So, we get a 2 x milli gram of protein; it is also possible that if we have more and more copies of the gene in the chromosomes, then it is possible that are proteins that had to be present at say, this level are now presented this level.
So, now, that would also lead to some amount of abnormality in the body, that would also lead to some amount of disease in the body. Next is translocation. So, a part of a chromosome has shifted to another chromosome. So, translocation and inversion, now in both of these situations your genes are there in the chromosome, whether in that particular chromosome or in some other chromosome. But then why are these important? Because these may break some of the genes.
So, for instance, if you had this DNA and in this DNA you had this portion as say a gene that is call it gene X. Now when this portion is getting inverted then it is possible that your inversion occurs at this region.
So, in the resulting chromosome you will have a situation in which your half of the gene is here, then this portion was inverted. So, now, when that inversion happens so this portion gets to this side and this portion get to this side. So, in that situation you will have that this portion has now turned into this side and is now here. Now what you are saying here is that, we have a fragment of gene X here and we have a fragment of gene X here. Now in the earlier situation, when you had the complete gene X, this was producing some protein, but now we have got two different fragments of gene X.
So, probably your protein is no longer been produced. Or it is also possible that, in these situations you may have, so for instance, this portion on the right it was having say, some other gene. So, now, this was say gene Y. When this inversion occurs, now you have a situation in which you have these two fragments here and these two fragments here.
So, now in place of your gene X, you have another portion of information. Let us call it gene X’ and let us call this one is gene Y’. Now there could be situations in which your gene X’ or gene Y’ are just non-functional so they are not producing anything or they are producing something that has minor amount of aberration, but then because this is coding for an entirely new sort of a protein, it is also possible that is produces some protein that is completely harmful to the body.
So, probably it produces a protein that goes and attaches itself to an enzyme and it stops the functioning of that enzyme. So, in those situations, the life of the animal would become much more critical. So, what are the impacts of these chromosomal abnormalities they depend on which genes are being impacted, the level to which they are being impacted, and also any new genes that get created in this manner. So, the impacts may vary, but then these are the basic chromosomal disorders that would lead to such an impact. (Refer Slide Time: 10:59)

Next we have genetic disorders. Now a genetic problem that is called by an abnormality or abnormalities in the genome. So, it is very similar to the chromosomal disorders but here we are looking at the genetic level.
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So, now, the kinds of genetic disorders could include a gene that does not work say, due to deletion or inactivation. Now deletion is something that we have already seen. So, essentially you had a gene X here. Now if this portion see got deleted so, now you would have a chromosome that was not have any gene X. So, that is deletion. But then what is inactivation.
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So, if you consider any gene, so this is your gene X that is producing a protein X. Now the amount of protein that needs to be produced in the body has to be very carefully regulated. So, for instance, if there is any enzyme that is being produced, if there is no enzyme or very little amount of enzyme then the body will not be able to function properly, but at the same time if this enzyme is present in a very large amount, then too it will not be able to function properly. Now to control that there are a number of activating and deactivating regions in the whole of the genome.
So, for instance, if you have this gene and if you have sequences before it that say, have Acetylation. So, Acetylation would mean that there are acetyls groups that get attached here. So, that would lead to an activation of this gene. On the other hand, if there are some groups that get Methylated, so Methylation is when you have your CH3, a group that it is attached here. So, in that case, your gene will become inactivated. So, Methylation leads to inactivation and Acetylation leads to activation of the gene.
So, if this gene is activated it will produce protein X, if this gene is inactivated it will not produce protein X. Now when your chromosomal abnormalities are leading to a situation in which your gene was not deleted, but it gets inactivated.
So, what is happening in this case is that, suppose in our previous example, we had this is gene X that was inactivated and your gene Y that was having an activation area here. Now once you have this translocation.

what we will observe is that, this region, the purple region now comes to the side because this side shifted to this side. Now in that case; and here your inactivation region remain as such, because this is outside the translocation region. Now in this case, what is happening is that, this gene X, that was earlier inactivated. Now this gene X’ also happens to be an inactivated gene, but then your gene Y that was activated, now does not have any of these activation sequences. So, your gene Y’, even if it is able to code for a correct protein, it will be inactivated in this case because it does not have the activation sequences before it.
So, it is a gene that does not work. Similarly, you can have a gene that works extra because that is present in multiple copies or there is an extra activation sequence that is present because of the genetic disorder. Or you can have a situation in which there is a gene that does different work say, due to mutation that changes the structure of the protein made. So, in this example, we had seen that are a gene Y had converted into gene Y’.
So now, this would be having a very different function and a very different sequence, but then it is also possible, that if you have a gene then there are some region that get changed and in that case this would also lead to a mutation.
So, your kinds of genetic disorders include, a gene that is not working, a gene that is doing an extra work, or gene that is doing a different work; making a very different protein. (Refer Slide Time: 15:20)

Now, let us have a look at Inbreeding. Inbreeding refers to the meeting of individuals that are genetically related. So, essentially, it means meeting of individual say, that are brothers and sisters or say, parents and children. So, that would called as an as a very extreme level of inbreeding. Now it increases homozygosity, causing expression of recessive traits and reduces variation between individuals in the population. Why? Because both of these individuals were genetically related so there is a high possibility that both of them are having the same genes in a number of locations. Now when both of these individuals mate together, then there is a high possibility that any of the recessive traits start showing themselves.
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So, as we had seen in our previous class, if you have a situation in which you have say, Ta Tb and Tc and Td. If these are four different alleles and you have these two individuals, then the progeny would be Ta Tc, Ta Td, Tb Tc, and Tb Td.
So, there would be these four different kinds of individuals, because both of these individuals the parents are not related so they are having very different alleles among themselves. But then, if both of these are related then you can have a situation in which you have Ta Tb crossed with Ta Tb. Now what would that result in? That result in Ta Ta Ta Tb, Ta Tb ,and Tb Tb. So, these are the four individuals that are formed when both of your parents are genetically related. So, they are having the same alleles, on this particular gene. Now if we look at the results we have the situation Ta Ta and Tb Tb.
these progeny; so now, in the previous situation, we did not have any gene that was homozygous. So, we did not have a situation with T a T a or T b T b or T c T c or T d T d, but in this situation, when our parents are genetically related, we have a situation in which the offspring is T a T a or the offspring is T b T b. Now why is it important this is important because say your T a or T b was a recessive allele.
So, in this case the phenotype will be that of T c in this case the phenotype will that be of T d, in this case, your phenotypes is T c and here your phenotype is T d. And if this these alleles are coding for say, some recessive disorder. So, let us say that only your T a was a recessive gene here. So, in this situation, these two individuals will be expressimg the phenotype of T b. So, here we are saying that T a is recessive.
So, these two individuals are showing the phenotype of T b because they are heterozygous. This one is homozygous, but it is still showing the phenotype of T b, but what happens in this case is that, this individual has not started showing up the phenotype that was coded by the T a gene or the T a allele. So, what is happening in this case is that, we are seeing an expression of a recessive trait that was not seen before. Now these recessive traits might be coding for some diseases.
Now this also reduces variation between individuals in the population, because what we are seeing here is that, in our second scenario, in this second scenario, we saw that both of these individuals were the same and if you look at their progeny, so this one is say coding for a recessive disorders so this dies off. So, now, in the second generation also we are seeing the same alleles in the same order that are seen in the next generation. And if this thing continues, then the amount of variation between the individuals we will go on reducing with every generation.
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Now, in some organisms, inbreeding is seen naturally. So, in the case of drosophila melanogaster or banded mongoose, the animals have a tendency to prepare meeting with one of their relatives. But then in the case of some other animal populations, they are forced into inbreeding when the population is so small and isolated that most of the individuals are already genetically related; there is not much of a meeting choice available for those animals.
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what are the impacts of inbreeding? Suppose you have a very small population; most of the individuals are already genetically related so, there is inbreeding. So, why should we be concerned about inbreeding? So, there are three kinds of changes that these can bring about; you can have same genes, you can have little variety, and you can have fixed alleles.
So, we will have a look at the impacts here. So, what we are observing is that there are a group of animals in which most of the animals have the same genes. So, essentially all the animals are very similar to being clones of each other.
So, what happens is that when animal gets a disease, the other animal can also get that disease very fast. Because the pathogen that was able to infect one organism will be very easy able to infect another organism, because the immune response that is being set up by both of these individuals are one and the same. Also, if there is a little variety and also there is there are fixed alleles. So fixed alleles is a situation in which; now coming back to example. Here we were observing situations in which all these, you have four different alleles in the population, but then what happens.
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If all your organisms are say T a T a crossed with T a T a. So, in this situation, all the progeny that are formed will be T a T a only.
So, in this situation, we will say that our allele T a has become fixed in the population, there is no way that we can have another allele in this population, till we get a mutation or till we get some other population from outside. So, these are known as fixed alleles. (Refer Slide Time: 21:51)

So, the impacts are seen in a number of ways such as Juvenile mortality. So, this is one paper in which they studied cheetahs with their stadbooks. A stadbook is a collection of the information of their parents and the children.
So, if you look at unrelated populations, we had in an infant mortality of 26.3 percent, but if you look at related organisms we had an infant mortality of 44.2 percent. So, the amount of infant mortality goes up.
Now, why does this go up? Because there could be a number of recessive diseases that are now showing up even in the embryonic stage and so this is one defence mechanism that nature has put up, in that if there is a foetus that is having a number of diseases then it automatically aborts itself. Or even if this foetus is able to come up to the stage where it is born, then because most of these disorders will start showing up at the early age so, we will see a huge amount of infant mortality. So, there will be more number of stillbirths and also more number of infant mortality.

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Now, a case study here is the case study of isle royal wolves. Now isle royal is an island in the United States and this island is surrounded by water on all sides and so, it is completely cut off from any other land mass. The only way in which it gets connected to the land masses is in the case of winter seasons where an ice bridge forms that connects it to the mainland. Now in the 19th century we had a situation in which some moose came into this island. And moose are very similar to our deers; they are large sized animals and they are herbivorous.
So, because there were no predators on this island so the moose population started increasing. Then in the early 1900’s we had some wolf that came into this island when another ice bridge found.
So, if you look at this blue coloured chart, this blue colours tells us the number of wolves and it goes from 0 to 50. The yellow colour chart tells us the number of moose and it goes from 0 to 2500. So, we have a very line number of herbivorous and a very less number of predators and on this islands. But if you look at these predators, these wolves, because a very small population came into this island and this small population was breeding among itself so we started seeing quite a lot of in breeding in this system.
So, what happened was that, we had this moose population and then we had this wolf population. Now wolf population would decline in certain times, because there is a severe winter and that could lead to death of wolves and also that of the moose. Now if you look at wolves chart. So, this wolves density this kept on increasing and by 1980 we had wolves that had reached the highest density that is found in nature. But then in 1981, there was a fisherman that visited this island together with his dog and that dog had canine parvo virus.
Now, this parvo virus was spread from that dog into the wolves and we can see that their population that reached to this height now suddenly decimated. Now why was this decimation possible because most of these wolves work closely related to each other and so if one wolves got infected, there was a very high chance that the other wolves also get infected. Now after this decimation they again started to increase their population, but then this population was kept at a very low pace because of huge amount of inbreeding depression.
So, essentially here we had very less number of wolves that had come inside and at this point we had another bottle neck in which most of individuals died of and so, a very less number of individuals for left so, any wolves from this point onwards would be having a very high level of inbreeding depression.
Now, when the wolf population is less the moose populations they starts to increase. And then there was a severe winter in 1996 in which we had a severe decimation in the moose population. Now in 1997 we had one individual that came in and that was known as the old gray guy. So, this individual was able to provide some amount of genetic rescue into the inbreed wolves and so, their population increased again. So, from this level it reached to this level. Then this individual also died off and then we had these wolves that were extremely closely related to each other.
So, this is a natural case study that has come up. Now, if we observe these Isle Royale wolves, what sorts of genetic abnormalities do you observe in these.
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So, one is a very high level of stillbirths. This stillbirth occurs because most of the foetuses have some amount of recessive disorders some diseases and so, nature expells them out nature aborts them. So, that these are not born with these diseases.
Now even in the case of the adult wolves. So, these are the wolves that were able to be born and then reach to their maturity, we can observe genetic disorders such as this opaque eye. Now if there is a wolf whose eye is opaque then it would not be able to hunt efficiently. And in this particular wolf population we are observing a number of wolves that are having opaque eyes which is another genetic disorder.
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Next we are observing disorders even in their skeletal systems. So, these are the last three wolves that remain in the system. And both of these are extremely closely related and this is the offspring and if you see the offspring then there is a hunchback in this wolf and this wolf is not able to hunt properly, it is not even able to walk properly. So, this is one case study.
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Now, the other kinds of abnormalities that we have observed in highly inbreed populations are things such as changes in the sperms. So, if we consider a sperm they would have a head region and a long flagellum.
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So, this is the structure of a sperm. But if you look at these cheetahs sperms which are very highly inbreed, we see abnormalities such as this. So this a micro cephalic sperm in which the head region is very small. Here we have a sperm that has got two heads. Here we have a sperm that has got two tails. So, we are observing genetic or structural abnormalities in a number of cheetahs that are closely inbreed.
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Other kinds of abnormalities that we observe; so, this is in the case of lions sperms because these animals; so, cheetahs and lions are heavily hunted in the past. So, most of the animals that are left out now are closely related. So, in the case of lions sperm as well, we are seeing things like macro cephalic i.e. large his head; micro cephalic i.e. small size head in this sperm, biflagellate, bicephalic and then we have abnormal acrosomes, abnormal midpiece tightly coiled Flagellum, which is not allowing these sperms to move, detached head so, your head is completely separated from the Flagellum, bent midpiece. So, in all the portions of the sperm we are now observing abnormalities. So now, this is also a result of the genetic disorder that have been brought about by inbreeding.
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Another case study is that of the spread of diseases. So, in May 1982, a clinically healthy 8 year old female cheetah in the Cheetah breeding program at Wildlife Safari, Oregon in the United States developed Jaundice fever and diarrhoea. And because it was there in a Cheetah breeding program facility so, it was treated aggressively. So, even with aggressive therapy including diuretics antibiotics, vitamins, steroids, and post feeding, the animal died in a week.
So, we had a healthy looking cheetah that suddenly developed jaundice fever and diarrhoea and then died in a week. The diagnosis was feline infectious peritonitis caused by a corona virus. Now into this was in May 1982 and this is a viral disease. So, now by January 1983 all the cheetahs at the facility had developed antibodies and during the year over 90 percent showed sign of the disease and 18 animals died. So, when we say that there is an animal that is showing that has developed antibodies, it means that the virus has infected that animal because of which the immune system is not putting up a response to the virus. So, this response is in the form of antibodies.
So, in say, around seven months we saw that all the cheetahs in the facility had been infected by the virus and in the year over 90 percent of these started showing signs of the disease and 18 animals died out. That is a very high level of mortality. Now if you have a high level of mortality there could be a number of reasons the most common reason is that we have a virus, that is extremely virulent and that has a very high level of lethality. So, this is something that we had discussed before whenever we are talking about a pathogen, we are looking at it is virulence we are looking at its lethality. Now in this situation, we could have a virus that had a very high level of virulence, a very high level of infectivity. So, infectivity which mean that it infects all the other animals. Virulence means that it shows signs of a disease that has a level of severity and then it also has a very high level of lethality because of which a number of animals are died out.
But if you look at some other evidences from this area then because this was already a facility so, the scientist took out fluid and tissue samples from the diseased animal and then injected them into kittens experimentally.

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So, if this virus was a virus that had a very high level of infectivity virulence and lethality, then the kitten should also have died because they are also closely related to the cheetahs they belong to the same feline family, but in this case these kittens did not get the disease.
So, this virus was not able to infect these kittens and when we are talking about kittens they already have a very small age. So, they are extremely young and we scientist is use kittens because very young animals and very old animals have higher susceptibility to be infected by the disease, but still it did not produce disease in the kittens. Also 10 African lions in the same facility did not develop signs of the disease.
So, lions are also members of the cat family and they were also in the same facility, but they also did not develop any signs of the disease. So, then it was figured out that the cheetahs, that were there in the facility, did not have a significant variation in the Major Histocompatibility Complex genetic makeup and all showed the same response to the virus. The major histocompatibility complex is a set of cells surface proteins that recognise foreign molecules and with little variation in the MHC genetic makeup the cheetahs immune system could not recognise many pathogens as foreign molecules. (Refer Slide Time: 33:38)

So, what was happening in this case is that, when you have a virus inside the body, you have an immune response that the disease gets treated by itself. Now when we talk about the immune response then this response could be against any new organism that has come into the body.